Skip to main content
PMC home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1999 Oct;58(10):630–634. doi: 10.1136/ard.58.10.630

Presentation of autoantibody to proliferating cell nuclear antigen in patients with chronic hepatitis B and C virus infection

B Tzang 1, T Chen 1, T Hsu 1, Y Liu 1, G Tsay 1
PMCID: PMC1752782  PMID: 10491362

Abstract

OBJECTIVES—To study the association of antibodies to proliferating cell nuclear antigen (PCNA) in patients with chronic hepatitis B (HBV) and C (HCV) virus infection.
METHODS—Sera from 243 patients with chronic HBV infection; 379 patients with chronic HCV infection; 80 patients with systemic lupus erythematosus (SLE); 28 patients with rheumatoid arthritis; 15 patients with Sjogren's syndrome; eight with polymyositis; eight with primary biliary cirrhosis; and 33 healthy control subjects were tested for the presentation of anti-PCNA antibodies by enzyme linked immunosorbent assay (ELISA) and immunoblotting using recombinant PCNA as antigen. The distribution of immunoglobulin isotypes of anti-PCNA antibody was measured by ELISA assay.
RESULTS—By ELISA, anti-PCNA antibodies were detected in 30 (12.3%) patients with chronic HBV infection, 71 (18.7%) patients with chronic HCV infection, and five (6.3%) patients with SLE. The inhibition of binding with these sera by purified PCNA was shown to exceed 71%. By immunoblotting, the frequency of anti-PCNA in patients with chronic HBV and HCV infection was 17 of 243 (7%) and 41 of 379 (11%), respectively. Absorption studies on indirect immunofluorescence showed the typical nuclear speckled staining pattern by anti-PCNA sera was abolished by preincubation of sera with PCNA. Anti-PCNA antibody was not detected in sera from patients with autoimmune diseases except SLE. Anti-PCNA antibodies in patients with chronic HBV and HCV infection were predominantly IgG.
CONCLUSION—These data suggest that anti-PCNA antibody are also present in patients with chronic HBV and HCV infection. Anti-PCNA antibody may not be specific for SLE.



Full Text

The Full Text of this article is available as a PDF (644.4 KB).

Figure 1  .

Figure 1  

Open in a new tab

Anti-PCNA antibody concentrations in patients with hepatitis B and C virus infection, different autoimmune diseases, and normal controls. Purified recombinant PCNA was used as antigen and determined by ELISA. Values above 0.842 were regarded as increased anti-PCNA. Anti-PCNA antibody was only present in the patients with hepatitis B and C infection and SLE.

Figure 2  .

Figure 2  

Open in a new tab

Reactivities of anti-PCNA on immunoblotting using recombinant PCNA proteins (A) and total CHO-K1 cells proteins (B) as antigens. Immunoblots of recombinant PCNA antigens (A) were probed with monoclonal anti-PCNA antibody (lane 2), and sera from patients with HCV infection (lanes 3-7). Immunoblots of total CHO-K1 cells proteins (B) were probed with monoclonal anti-PCNA antibody (lane 1), sera from patients with HBV infection (lanes 2-4), and normal control (lane 5). Sera from patients HBV and HCV infection and monoclonal anti-PCNA antibody reacted with a band of molecular weight of 34 kDa.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abu-Shakra M., El-Sana S., Margalith M., Sikuler E., Neumann L., Buskila D. Hepatitis B and C viruses serology in patients with SLE. Lupus. 1997;6(6):543–544. doi: 10.1177/096120339700600612. [DOI] [PubMed] [Google Scholar]
  2. Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
  3. Bootsma H., Spronk P. E., Ter Borg E. J., Hummel E. J., de Boer G., Limburg P. C., Kallenberg C. G. The predictive value of fluctuations in IgM and IgG class anti-dsDNA antibodies for relapses in systemic lupus erythematosus. A prospective long-term observation. Ann Rheum Dis. 1997 Nov;56(11):661–666. doi: 10.1136/ard.56.11.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bravo R., Celis J. E. A search for differential polypeptide synthesis throughout the cell cycle of HeLa cells. J Cell Biol. 1980 Mar;84(3):795–802. doi: 10.1083/jcb.84.3.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bravo R., Frank R., Blundell P. A., Macdonald-Bravo H. Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature. 1987 Apr 2;326(6112):515–517. doi: 10.1038/326515a0. [DOI] [PubMed] [Google Scholar]
  6. Buskila D., Sikuler E., Shoenfeld Y. Hepatitis C virus, autoimmunity and rheumatic disease. Lupus. 1997;6(9):685–689. doi: 10.1177/096120339700600902. [DOI] [PubMed] [Google Scholar]
  7. Colaço C. B., Mackie I. J., Irving W., Machin S. J. Anti-cardiolipin antibodies in viral infection. Lancet. 1989 Mar 18;1(8638):622–622. doi: 10.1016/s0140-6736(89)91658-9. [DOI] [PubMed] [Google Scholar]
  8. Colaço C. B., Male D. K. Anti-phospholipid antibodies in syphilis and a thrombotic subset of SLE: distinct profiles of epitope specificity. Clin Exp Immunol. 1985 Feb;59(2):449–456. [PMC free article] [PubMed] [Google Scholar]
  9. Daidoji H., Takasaki Y., Nakane P. K. Proliferating cell nuclear antigen (PCNA/cyclin) in plant proliferating cells: immunohistochemical and quantitative analysis using autoantibody and murine monoclonal antibodies to PCNA. Cell Biochem Funct. 1992 Jun;10(2):123–132. doi: 10.1002/cbf.290100209. [DOI] [PubMed] [Google Scholar]
  10. Fox R. I., Robinson C. A., Curd J. G., Kozin F., Howell F. V. Sjögren's syndrome. Proposed criteria for classification. Arthritis Rheum. 1986 May;29(5):577–585. doi: 10.1002/art.1780290501. [DOI] [PubMed] [Google Scholar]
  11. Fritzler M. J., McCarty G. A., Ryan J. P., Kinsella T. D. Clinical features of patients with antibodies directed against proliferating cell nuclear antigen. Arthritis Rheum. 1983 Feb;26(2):140–145. doi: 10.1002/art.1780260204. [DOI] [PubMed] [Google Scholar]
  12. Hansen K. E., Arnason J., Bridges A. J. Autoantibodies and common viral illnesses. Semin Arthritis Rheum. 1998 Apr;27(5):263–271. doi: 10.1016/s0049-0172(98)80047-4. [DOI] [PubMed] [Google Scholar]
  13. Hsu H. Y., Chang M. H., Chen D. S., Lee C. Y., Sung J. L. Baseline seroepidemiology of hepatitis B virus infection in children in Taipei, 1984: a study just before mass hepatitis B vaccination program in Taiwan. J Med Virol. 1986 Apr;18(4):301–307. doi: 10.1002/jmv.1890180402. [DOI] [PubMed] [Google Scholar]
  14. Huff J. P., Roos G., Peebles C. L., Houghten R., Sullivan K. F., Tan E. M. Insights into native epitopes of proliferating cell nuclear antigen using recombinant DNA protein products. J Exp Med. 1990 Aug 1;172(2):419–429. doi: 10.1084/jem.172.2.419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Inman R. D. Rheumatic manifestations of hepatitis B virus infection. Semin Arthritis Rheum. 1982 May;11(4):406–420. doi: 10.1016/0049-0172(82)90028-2. [DOI] [PubMed] [Google Scholar]
  16. Kurki P., Vanderlaan M., Dolbeare F., Gray J., Tan E. M. Expression of proliferating cell nuclear antigen (PCNA)/cyclin during the cell cycle. Exp Cell Res. 1986 Sep;166(1):209–219. doi: 10.1016/0014-4827(86)90520-3. [DOI] [PubMed] [Google Scholar]
  17. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  18. Liu Y. C., Bambara R. A. Gene expression of PCNA/cyclin in adult tissues and the R3230AC mammary tumor of rat. Biochem Biophys Res Commun. 1989 Jun 15;161(2):873–882. doi: 10.1016/0006-291x(89)92681-8. [DOI] [PubMed] [Google Scholar]
  19. Miyachi K., Fritzler M. J., Tan E. M. Autoantibody to a nuclear antigen in proliferating cells. J Immunol. 1978 Dec;121(6):2228–2234. [PubMed] [Google Scholar]
  20. Murashima A., Takasaki Y., Ohgaki M., Hashimoto H., Shirai T., Hirose S. Activated peripheral blood mononuclear cells detected by murine monoclonal antibodies to proliferating cell nuclear antigen in active lupus patients. J Clin Immunol. 1990 Jan;10(1):28–37. doi: 10.1007/BF00917495. [DOI] [PubMed] [Google Scholar]
  21. Ohata N. [Clinical significance of antibodies to proliferating cell nuclear antigen (PCNA)]. Ryumachi. 1987 Apr;27(2):79–87. [PubMed] [Google Scholar]
  22. Prelich G., Stillman B. Coordinated leading and lagging strand synthesis during SV40 DNA replication in vitro requires PCNA. Cell. 1988 Apr 8;53(1):117–126. doi: 10.1016/0092-8674(88)90493-x. [DOI] [PubMed] [Google Scholar]
  23. Prieto J., Yuste J. R., Beloqui O., Civeira M. P., Riezu J. I., Aguirre B., Sangro B. Anticardiolipin antibodies in chronic hepatitis C: implication of hepatitis C virus as the cause of the antiphospholipid syndrome. Hepatology. 1996 Feb;23(2):199–204. doi: 10.1002/hep.510230201. [DOI] [PubMed] [Google Scholar]
  24. Rubin R. L., Joslin F. G., Tan E. M. An improved ELISA for anti-native DNA by elimination of interference by anti-histone antibodies. J Immunol Methods. 1983 Oct 28;63(3):359–366. doi: 10.1016/s0022-1759(83)80009-x. [DOI] [PubMed] [Google Scholar]
  25. Schattner A., Rager-Zisman B. Virus-induced autoimmunity. Rev Infect Dis. 1990 Mar-Apr;12(2):204–222. doi: 10.1093/clinids/12.2.204. [DOI] [PubMed] [Google Scholar]
  26. Strassburg C. P., Manns M. P. Autoimmune hepatitis versus viral hepatitis C. Liver. 1995 Oct;15(5):225–232. doi: 10.1111/j.1600-0676.1995.tb00676.x. [DOI] [PubMed] [Google Scholar]
  27. Takasaki Y., Deng J. S., Tan E. M. A nuclear antigen associated with cell proliferation and blast transformation. J Exp Med. 1981 Dec 1;154(6):1899–1909. doi: 10.1084/jem.154.6.1899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Takasaki Y., Fishwild D., Tan E. M. Characterization of proliferating cell nuclear antigen recognized by autoantibodies in lupus sera. J Exp Med. 1984 Apr 1;159(4):981–992. doi: 10.1084/jem.159.4.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tan E. M. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989;44:93–151. doi: 10.1016/s0065-2776(08)60641-0. [DOI] [PubMed] [Google Scholar]
  30. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  31. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vaarala O., Palosuo T., Kleemola M., Aho K. Anticardiolipin response in acute infections. Clin Immunol Immunopathol. 1986 Oct;41(1):8–15. doi: 10.1016/0090-1229(86)90046-2. [DOI] [PubMed] [Google Scholar]
  33. Williamson J. M., Chalmers D. M., Clayden A. D., Dixon M. F., Ruddell W. S., Losowsky M. S. Primary biliary cirrhosis and chronic active hepatitis: an examination of clinical, biochemical, and histopathological features in differential diagnosis. J Clin Pathol. 1985 Sep;38(9):1007–1012. doi: 10.1136/jcp.38.9.1007. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES